Background and aim of the study: Calcific aortic stenosis (AS) is the most frequently acquired valvular disease of the elderly in the Western world. A genetic background for AS has been proposed. The deposition of calcium hydroxyapatite is the key problem of valve calcification; vitamin D and parathyroid hormone are major factors in calcium homeostasis. The vitamin D receptor (VDR) gene and parathyroid hormone (PTH) gene variants were selected as candidate genes.
Methods: A total of 538 patients with severe calcific AS (identified echocardiographically) were characterized by left heart catheterization. A group of 536 patients in whom heart disease had been excluded by left heart catheterization served as a control population. The cardiovascular risk profile was assessed, and three gene variants were analyzed, namely VDR rs1544410, VDR rs1073810, and PTH rs6254.
Results: Patients with AS were found to have a higher prevalence of the PTH AA genotype (108 +/- 20.1% versus 71 +/- 13.2%; p = 0.007), while the VDR gene revealed a marginal, but statistically non-significant, association. The age and risk profile was similar in both groups.
Conclusion: To date, the association of the PTH gene variant has been the only positive association studied in patients with AS in a large population. Hence, the polymorphism is within an intron; the molecular mechanisms of altered gene expression should undergo further investigation.